A Phase 1 Study of ADI-001 in B Cell Malignancies

Phase 1

Recruiting

• Conditions: Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Marginal Zone Lymphoma; Primary Mediastinal B-cell Lymphoma; Diffuse Large B Cell Lymphoma; Lymphoma, Follicular
• Interventions: Genetic: ADI-001; Drug: Fludarabine; Drug: Cyclophosphamide

• Registration Number: NCT04735471
• Lead Sponsor: Adicet Therapeutics

Brief Summary

This is a Phase 1 dose escalation study following a 3+3 study design. The purpose of this study is to evaluate the safety and efficacy of ADI-001 in patients with B cell malignancies.

Detailed Description

ADI-001 is an investigational immunotherapy composed of allogeneic gamma delta T cells that is being evaluated as a potential treatment for patients diagnosed with B cell malignancies who have relapsed or are refractory to at least two prior regimens. This first-in-human study will assess the safety and tolerability of ADI-001 and is designed to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD). Patients will be administered a single infusion or multiple infusions of ADI-001 cells. The study will include the following two parts:

Part 1 : dose escalation and extension. Parts 1a (escalation) and 1b (extension) will involve escalation and administration of single dose of ADI-001 and multiple doses of ADI-001.

Part 2 : dose expansion will involve dose administration of ADI-001 at MTD/MAD as determined in Part 1.

The study will also assess the pharmacokinetics and pharmacodynamics of ADI-001.

Study Timeline

• Study First Submitted: 2021-01-26
• Study First Submitted QC: 2021-01-28
• Study First Posted: 2021-02-03
• Study Start: 2021-03-04
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-09
• Last Update Posted: 2024-04-10
• Primary Completion: 2025-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

1. Relapsed/refractory (R/R) previously treated B cell malignancies.
2. Prior treatment must include at least 2 prior regimens, including anti CD20 antibody therapies. Prior Treatment with CD19 CAR T may be considered.
3. Documented measurable disease as defined by Lugano 2014
4. Male or female ≥ 18 years of age
5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
6. Adequate hematological, renal, pulmonary, cardiac, and liver function
7. Female patients who are not pregnant or breastfeeding
8. Female patients of childbearing potential and all male patients must agree to use highly effective methods of birth control for the duration of the study.

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Exclusion Criteria

1. Current or history of any of the following conditions:

   1. Central nervous system (CNS) primary lymphoma (current or history)
   2. Unrelated malignancy requiring systemic treatment (current or history [in the past 3 years, other than hormonal treatment which is allowed])

2. Any of the following current conditions:

   1. Active acute or chronic graft versus host disease (GvHD) other than grade 1 with skin involvement, or GvHD requiring immunosuppressive treatment within 4 weeks of enrollment
   2. Any other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration
   3. Tumor mass effects such as bowel obstruction or blood vessel compression that require therapy
   4. Opportunistic infections

3. History of any clinically significant conditions in the opinion of the Investigator

4. Prior treatment with any of the following:

   a Gene therapy, genetically modified cell therapy, or adoptive T cell therapy within 6 weeks of study enrollment.

   b Radiation therapy within 4 weeks prior to study entry. Palliative local radiation may be allowed within 1 week prior to study entry.

   c Autologous stem cell transplant (SCT) within 6 weeks of planned ADI 001 infusion.

   d Allogeneic transplant and donor lymphocyte infusion within 3 months of planned CAR T cell infusion

5. Patients unwilling to participate in an extended safety monitoring period (long term follow up [LTFU] protocol)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ADI-001 Dose Escalation	ADI-001	ADI-001 is administered via infusion with ascending dose levels as a single dose to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) of ADI-001 (Part 1a).
ADI-001 Dose Escalation	Fludarabine	ADI-001 is administered via infusion with ascending dose levels as a single dose to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) of ADI-001 (Part 1a).
ADI-001 Dose Extension	ADI-001	ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).
ADI-001 Dose Expansion	Fludarabine	Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).
ADI-001 Dose Extension	Fludarabine	ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).
ADI-001 Dose Expansion	ADI-001	Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).
ADI-001 Dose Expansion	Cyclophosphamide	Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).
ADI-001 Dose Extension	Cyclophosphamide	ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).
ADI-001 Dose Escalation	Cyclophosphamide	ADI-001 is administered via infusion with ascending dose levels as a single dose to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) of ADI-001 (Part 1a).

Primary Outcome Measures

Name	Time	Method
Proportion of treatment emergent and treatment related adverse events	1 year	This primary endpoint will be used to determine the MTD/MAD of ADI-001
The Incidence of Subjects with Dose Limiting Toxicities within each dose level cohort	Day 28	This primary endpoint will be used to determine the Maximum Tolerated Dose (MTD) or Maximum Assessed dose (MAD).

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival	Day 28, Month 3, 6, 9, and 12
Time To Progression	Day 28, Month 3, 6, 9, and 12
Overall Survival	Day 28, Month 3, 6, 9, and 12
Frequency and persistence of ADI-001	Day 1 through Month 12	Defined as duration from Day 1 to undetectable levels of ADI-001 cells per microliter blood
Duration of Response	Day 28, Month 3, 6, 9, and 12
Overall Response Rate by Lugano Criteria	Day 28, Month 3, 6, 9, and 12

Trial Locations

Locations (10)

Baylor Scott & White Research Institute; 🇺🇸 Dallas, Texas, United States

Stanford University Medical Center; 🇺🇸 Stanford, California, United States

University of Miami- Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

Northside Hospital Blood and Marrow Transplant Group of Georgia; 🇺🇸 Atlanta, Georgia, United States

The State University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Swedish Cancer Center; 🇺🇸 Seattle, Washington, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States